The purpose of this study was to investigate the antiangiogenic
and in vivo properties of the recently identified
phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor Inositol(
1,3,4,5,6) pentakisphosphate [Ins(1,3,4,5,6)P5]. Because
activation of the PI3K/Akt pathway is a crucial step in
some of the events leading to angiogenesis, the effect of
Ins(1,3,4,5,6)P5 on basic fibroblast growth factor (FGF-2)–
induced Akt phosphorylation, cell survival, motility, and
tubulogenesis in vitro was tested in human umbilical vein
endothelial cells (HUVEC). The effect of Ins(1,3,4,5,6)P5 on
FGF-2-induced angiogenesis in vivo was evaluated using s.c.
implanted Matrigel in mice. In addition, the effect of
Ins(1,3,4,5,6)P5 on growth of ovarian carcinoma SKOV-3
xenograft was tested. Here, we show that FGF-2 induces Akt
phosphorylation in HUVEC resulting in antiapoptotic effect
in serum-deprived cells and increase in cellular motility.
Ins(1,3,4,5,6)P5 blocks FGF-2-mediated Akt phosphorylation
and inhibits both survival and migration in HUVEC.
Moreover, Ins(1,3,4,5,6)P5 inhibits the FGF-2-mediated capillary
tube formation of HUVEC plated on Matrigel and the
FGF-2-induced angiogenic reaction in BALB/c mice. Finally,
Ins(1,3,4,5,6)P5 blocks the s.c. growth of SKOV-3 xenografted
in nude mice to the same extent than cisplatin and it
completely inhibits Akt phosphorylation in vivo. These data
definitively identify the Akt inhibitor Ins(1,3,4,5,6)P5 as a
specific antiangiogenic and antitumor factor. Inappropriate
activation of the PI3K/Akt pathway has been linked to the
development of several diseases, including cancer, making
this pathway an attractive target for therapeutic strategies.
In this respect, Ins(1,3,4,5,6)P5, a water-soluble, natural
compound with specific proapoptotic and antiangiogenic
properties, might result in successful anticancer therapeutic
strategies.

The purpose of this study was to investigate the antiangiogenic
and in vivo properties of the recently identified
phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor Inositol(
1,3,4,5,6) pentakisphosphate [Ins(1,3,4,5,6)P5]. Because
activation of the PI3K/Akt pathway is a crucial step in
some of the events leading to angiogenesis, the effect of
Ins(1,3,4,5,6)P5 on basic fibroblast growth factor (FGF-2)–
induced Akt phosphorylation, cell survival, motility, and
tubulogenesis in vitro was tested in human umbilical vein
endothelial cells (HUVEC). The effect of Ins(1,3,4,5,6)P5 on
FGF-2-induced angiogenesis in vivo was evaluated using s.c.
implanted Matrigel in mice. In addition, the effect of
Ins(1,3,4,5,6)P5 on growth of ovarian carcinoma SKOV-3
xenograft was tested. Here, we show that FGF-2 induces Akt
phosphorylation in HUVEC resulting in antiapoptotic effect
in serum-deprived cells and increase in cellular motility.
Ins(1,3,4,5,6)P5 blocks FGF-2-mediated Akt phosphorylation
and inhibits both survival and migration in HUVEC.
Moreover, Ins(1,3,4,5,6)P5 inhibits the FGF-2-mediated capillary
tube formation of HUVEC plated on Matrigel and the
FGF-2-induced angiogenic reaction in BALB/c mice. Finally,
Ins(1,3,4,5,6)P5 blocks the s.c. growth of SKOV-3 xenografted
in nude mice to the same extent than cisplatin and it
completely inhibits Akt phosphorylation in vivo. These data
definitively identify the Akt inhibitor Ins(1,3,4,5,6)P5 as a
specific antiangiogenic and antitumor factor. Inappropriate
activation of the PI3K/Akt pathway has been linked to the
development of several diseases, including cancer, making
this pathway an attractive target for therapeutic strategies.
In this respect, Ins(1,3,4,5,6)P5, a water-soluble, natural
compound with specific proapoptotic and antiangiogenic
properties, might result in successful anticancer therapeutic
strategies.